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BIOCRYST’s FACTOR D PROTEIN GOING ALOFT; APRIL 24 SPACE SHUTTLE

Executive Summary

BIOCRYST's FACTOR D PROTEIN GOING ALOFT; APRIL 24 SPACE SHUTTLE launch of the Discovery (rescheduled after an April 12 technical malfunction) will carry four pharmaceutical protein crystal growth experiments on board, including one from the Birmingham, Alabama-based X-ray crystallography drug design firm, BioCryst. The company's co-founder Charles Bugg, PhD, is the director of the Center for Macromolecular Crystallography at the University of Alabama, Birmingham, which is coordinating the shuttle experiments. The Factor D project, to be conducted over the five-day flight of Discovery, will attempt to grow well-defracted protein crystals of the enzyme in the shuttle's microgravity environment. Previous space flights have demonstrated that crystals grown in space are larger and more well-formed than those grown on Earth. The flight will also carry agricultural protein crystal growth experiments. Factor D controls the release of inflammatory mediators by the immune system. Space-grown crystals of Factor D will be used in X-ray crystallography to create a selective inhibitor for the enzyme as the basis for designing a drug that may limit damage from stroke, coronary bypass surgery or kidney dialysis, BioCryst said. The experiments will be the seventh set of studies to be conducted on space shuttle flights under the auspices of the Center for Macromolecular Crytallography. As companies get more experience with the project, some participants are hoping for better results than in previous flights. Others are finding that space does not offer meaningful advantages. For example, some of the projects on board the Columbia at its Dec. 18 launch ("The Pink Sheet" Dec. 11, T&G-5) were adversely affected by temperature control problems in the bay where they were located. On the other hand, Burroughs Wellcome's reverse transcriptase crystal-growth experiments produced larger and more well-defined crystals than on a previous November 1988 space shuttle flight; however, the crystals were not superior to Earth-grown ones, the company said. In addition to Factor D, other crystals to be grown on board the shuttle flight include Vertex's porcine pancreatic elastase, which is being studied for its association with emphysema. Merck has been a sponsor for the product on earlier space shuttles. Vertex, a Cambridge, Mass.-based drug design R&D firm, described the Discovery project as a "model" for crystal-growth to "work out the kinks." The company will be sending other proteins into space in future shuttle flights. Other compounds under evaluation include malic enzyme, which Upjohn is looking at as a potential key to developing anthelmintics. Malic enzyme is important in the metabolic pathway of parasitic nematodes, Center for Macromolecular Crystallography Associate Director for Commercial Development Larry DeLucas explained. The space shuttle will also carry Eastman Kodak's carboxyl ester hydrolase, which is involved in the breakdown of fat. The crystal-growing experiment will be valuable in determining how fats and related enzymes are metabolized, DeLucas said. Schering-Plough was slated to send along another gamma interferon project -- one was included on the December Columbia flight -- but is now slated to place a gamma interferon experiment aboard the next scheduled shuttle flight in November.
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